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Grander, Christoph; Adolph, Timon E; Wieser, Verena; Lowe, Patrick; Wrzosek, Laura; Gyongyosi, Benedek; Ward, Doyle V; Grabherr, Felix; Gerner, Romana R; Pfister, Alexandra; Enrich, Barbara; Ciocan, Dragos; Macheiner, Sophie; Mayr, Lisa; Drach, Matthias; Moser, Patrizia; Moschen, Alexander R; Perlemuter, Gabriel; Szabo, Gyongyi; Cassard, Anne Marie; Tilg, Herbert
Gut, 05/2018, Volume: 67, Issue: 5Journal Article
Alcoholic liver disease (ALD) is a global health problem with limited therapeutic options. Intestinal barrier integrity and the microbiota modulate susceptibility to ALD. , a Gram-negative intestinal commensal, promotes barrier function partly by enhancing mucus production. The aim of this study was to investigate microbial alterations in ALD and to define the impact of administration on the course of ALD. The intestinal microbiota was analysed in an unbiased approach by 16S ribosomal DNA (rDNA) sequencing in a Lieber-DeCarli ALD mouse model, and faecal abundance was determined in a cohort of patients with alcoholic steatohepatitis (ASH). The impact of on the development of experimental acute and chronic ALD was determined in a preventive and therapeutic setting, and intestinal barrier integrity was analysed. Patients with ASH exhibited a decreased abundance of faecal when compared with healthy controls that indirectly correlated with hepatic disease severity. Ethanol feeding of wild-type mice resulted in a prominent decline in abundance. Ethanol-induced intestinal depletion could be restored by oral supplementation. Furthermore, administration when performed in a preventive setting decreased hepatic injury, steatosis and neutrophil infiltration. also protected against ethanol-induced gut leakiness, enhanced mucus thickness and tight-junction expression. In already established ALD, used therapeutically ameliorated hepatic injury and neutrophil infiltration. Ethanol exposure diminishes intestinal abundance in both mice and humans and can be recovered in experimental ALD by oral supplementation. promotes intestinal barrier integrity and ameliorates experimental ALD. Our data suggest that patients with ALD might benefit from supplementation.
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